FDA Approves IV Fosfomycin for Complicated UTIs
The U.S. FDA has approved intravenous fosfomycin (Contepo) for treating adults with complicated urinary tract infections (cUTI), including acute pyelonephritis, caused by susceptible E. coli and Klebsiella pneumoniae, as announced by Meitheal Pharmaceuticals.
CONTEPO, an intravenous (IV) antibiotic that is an injectable epoxide and sole antibiotic class member, has demonstrated activity against gram-negative bacteria including Escherichia coli and Klebsiella pneumoniae that cause cUTIs.1,2 It has no known cross-resistance to other antibiotic classes.3,4 Targeting bacteria’s cell wall at an earlier stage than β-lactam antibiotics, CONTEPO’s unique mechanism of action inhibits the first committed step in bacterial cell wall synthesis, eliminating all downstream signaling that is vital to cell survival and leading to the destruction of the bacteria.
“The escalating public health issue of antimicrobial resistance and emergence of highly resistant organisms demands immediate attention and innovative therapeutic solutions. The approval of CONTEPO is a major milestone in our company’s evolution and the fight against the ongoing threat of antibiotic resistance,” said Tom Shea, Chief Executive Officer of Meitheal Pharmaceuticals. “We are proud to add a second branded product to our growing portfolio of anti-infectives and antibiotics and look forward to delivering this high-quality and effective antibiotic medicine to patients and providers.”
The FDA approval is supported by data from the pivotal Phase 2/3 ZEUS (ZTI-01) trial which investigated the safety and efficacy of the treatment on hospitalized patients with cUTI, including acute pyelonephritis. The trial showed that intravenous (IV) fosfomycin was noninferior to piperacillin/tazobactam for the primary efficacy endpoint—overall success, defined as clinical cure and microbiologic eradication—at the test-of-cure visit in the microbiological modified intent-to-treat (mMITT) population. Overall success was achieved in 63.5% (108/170) of patients receiving IV fosfomycin and 55.6% (94/169) of those receiving piperacillin/tazobactam, with a treatment difference of 7.9 (95% CI -3.1 to 18.9).
The safety and tolerability profile of CONTEPO was generally well-tolerated.2 The most commonly reported adverse reactions in ≥2% of CONTEPO patients in the study included transaminase elevations (10.3%), hypokalemia (9.9%), neutropenia (6.4%), nausea (4.3%), diarrhea (3.9%), vomiting (3.9%), hypocalcemia (3.9%), hypernatremia (3.4%), headache (2.6%), and hypophosphatemia (2.1%).
"The rise of multi-drug-resistant pathogens poses a significant threat to our ability to combat infectious diseases, underscoring the continued need for novel therapies that target resistant organisms in patients having cUTIs," said Dr. Keith S. Kaye, MD, MPH Chief, Division of Allergy, Immunology and Infectious Diseases at the Robert Wood Johnson Medical School.
“With an estimated three million cases of cUTIs treated in the hospital setting annually, there is a critical need for a safe and effective treatment option.5 CONTEPO’s safety, efficacy, and novel mechanism of action makes it a favorable new treatment option,” said Dr. Keith Robinson, Chief Medical Officer of Meitheal Pharmaceuticals.
With this approval, Meitheal’s portfolio has rapidly expanded to over 70 on-market products with additional generic launches expected before the end of the year across its core therapeutic areas of anti-infectives, anesthetics, critical care, fertility, and oncology.
ABOUT CONTEPO
CONTEPO (fosfomycin) for injection is a novel, intravenous antibiotic and is the only FDA approved epoxide antibacterial product. Part of a different class of antibiotics known as phosphonics, CONTEPO covalently binds and inhibits phosphoenolpyruvate transferase (MurA) which prevents the formation of cell wall precursors, blocks cell wall synthesis and leads to the destruction of bacteria. It has demonstrated activity against gram-negative bacteria including Escherichia coli and Klebsiella pneumoniae and other antimicrobial resistant pathogens. Efficacy and safety in patients have been demonstrated in adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis.
